Hypolipemic activity of clofibrate-related compounds

Ethyl-2(p-chlorophenoxy)-2-methylpropionate (clofibrate) related compounds were synthesized from substituted aryloxy acetic acids (III) either by esterification with selected alcohols (3,3,5-trimethylcyclohexanol and oxyalkyltheophyllines), by introduction into heterocyclic ring system (triazine type) or by amidation (aminotriazines and p-aminobenzoates). Lipid lowering effect was tested in normolipemic and hyperlipemic rats against clofibrate as reference. Some of these derivatives show high activity at low dosage, even under hyperlipemic conditions, whereas clofibrate is only slightly effective. From pharmacological results it can be suggested that the nature of acid group substituent is the main factor for efficacy, while the role of alpha-substituent is important for differentiation of activity against cholesterol and/or triglyceride.